Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study

Abstract

PURPOSE The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses. METHODS This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13. RESULTS Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex. CONCLUSION This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care.

Systemic Therapy Is Associated with Improved Oncologic Outcomes in Resectable Stage II/III Intrahepatic Cholangiocarcinoma: An Examination of the National Cancer Database over the Past Decade

“…Patients who were stage I and underwent resection with negative margins did not experience longer OS when treated with AT compared to surgery alone. Our findings are consistent with previously published studies [ 18 , 43 ], but given the mixed results reported in the literature and the retrospective nature of the current study, future prospective trials are needed to investigate this finding further.…”

Current Trends in Inpatient Care and In-Hospital Mortality of Cholangiocarcinoma in Germany: A Systematic Analysis between 2010 and 2019

“…In our study, however, systematic chemotherapy is by far the most common treatment modality with a continuous and stepwise increase in the last years. This increase is most probably due to the introduction of new indications for systemic treatment in the context of CCA such as adjuvant treatment after complete tumor resection [ 12 ] and new second line treatment options [ 13 , 14 ] as well as novel molecular guided treatments [ 15 ]. A very similar trend was observed for surgical resection as well as for SIRT, while, interestingly, the number of photodynamic therapies significantly decreased from 2010 to 2019.…”

Role of the PP2A Pathway in Cholangiocarcinoma: State of the Art and Future Perspectives

“…Despite treatment advances in the last decade, patient outcomes are still very poor, with the 5-year survival rate below 20% [ 1 ]. Only 20–30% of cholangiocarcinoma will be diagnosed at a resectable stage; despite surgery and adjuvant treatment, the relapse rate remains high [ 2 ]. Thus, the majority of patients diagnosed with cholangiocarcinoma will, at some point in their journey, receive treatment with a palliative aim for advanced or recurrent disease.…”